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EditorEnzymatic autoimmune diseases, including lupus erythematosus, rheumatoid arthritis, Sjogren’s syndrome and multiple sclerosis, refer to the body’s own immune system that produces a large amount of resistance under the synergistic induction of certain genetic factors and external factors.
Specific antibodies and cells for autoantigens, which attack the body's own cells, organs and systems and cause pathogenic damage
.
Such diseases affect nearly 10% of the world's population, seriously affecting the quality of life of patients, and severe cases can be fatal
.
Immune cells, especially B lymphocytes, play a key role in the pathogenesis of autoimmune diseases
.
However, the molecular regulation mechanism of pathogenic self-reactive B lymphocytes in the initial development stage is still poorly understood
.
Glycosylation is the main method of protein post-translational modification
.
N-type sugars and O-type sugars are the main glycosylation types of cell surface proteins, and their sugar-based components are affected by cell development stages and changes in the environment
.
Cosmc and Tsynthase are the key molecules in O-sugar synthesis pathway, knocking out either of them can completely block the synthesis and extension of O-sugar
.
In the context of autoimmune diseases, it can be expected that changes in B cell surface glycosylation will affect the induction and development of autoimmune diseases, but there has been no relevant research before
.
The Richard Cummings laboratory of the Harvard Medical School Beth Israel Deaconess Medical Center (BIDMC) published a research article titled Cosmc deficiency causes spontaneous autoimmunity by breaking B cell tolerance in Science Advances on October 6, 2021.
This study clarified B for the first time.
O-type glycation on the surface of lymphocytes is the regulation mechanism of autoimmune diseases.
Its absence breaks the immune tolerance of B lymphocytes and triggers the spontaneous development of autoimmune diseases
.
Previously, the Cummings research group had used the Cre-LoxP system to establish BC-CsomcKO mice, in which Cosmc was only deleted in B cells
.
The author found that Cosmc controls the development and homing of B cells (Zeng et al, Nat Commun.
2020)
.
In the current study, the authors further found that in BC-CosmcKO mice, a variety of lesions similar to the symptoms of human autoimmune diseases can be observed, including body weight loss, swelling and inflammation of the spleen and multiple lymph nodes, and multiple organs, including eyes.
Damage and necrosis of the body, liver and skin
.
Interestingly, this kind of disease mostly occurs in female BC-CosmcKO mice, and the sex-differentiated characteristics of this kind of disease are similar to many human autoimmune diseases
.
These lesions eventually led to the death of approximately 10% of female BC-CosmcKO mice
.
The author further used a variety of methods to prove that there are a variety of high-level expression of anti-autoantigen antibodies in BC-CosmcKO mice, and the downstream immune effectors and effector mechanisms have signs of activation, which shows that the absence of Cosmc breaks the B cell immune tolerance
.
The destruction of B cell tolerance is usually accompanied by a series of B cell development and dysfunction
.
The author further found that Cosmc-deficient B lymphocytes overreacted to a variety of antigens and combinations of antigens
.
Related to the excessive activation of Cosmc-deficient B lymphocytes is the presence of a high proportion of spontaneous germinal center B cells in a variety of lymphoid tissues in BC-CosmcKO mice, which is five to ten times higher than that of normal wild type.
In some lymphoid tissues, more than half of the B cells are germinal center B cells
.
Finally, the author analyzes the impact of the absence of Cosmc in B cells on the signal transduction of B cell receptors at the molecular level
.
It was found that the loss of Cosmc leads to an increase in the retention time of the B cell receptor (IgM) on the cell surface, which enhances a variety of downstream transduction signals
.
This indicates that the O-sugar on the cell surface controlled by Cosmc maintains its downstream signal homeostasis by regulating the endocytosis of B cell receptors under physiological conditions
.
The lack of O-type sugars, as demonstrated by the B cells of BC-CosmcKO mice, leads to the loss of B cell signal transduction and eventually various pathologies
.
Since O-sugar is easily affected by the environment, it is worth exploring whether there is a similar phenomenon in patients with autoimmune diseases
.
Richard Cummings is the titled professor of S.
Daniel Abraham of BIDMC at Harvard Medical School.
His team cloned and analyzed the Tsynthase and Cosmc genes many years ago
.
Dr.
Junwei Zeng, lecturer in the Department of Surgery, is the first author and corresponding author of the article
.
The author found for the first time that the deletion of a single gene (Cosmc) in B lymphocytes can lead to the spontaneous development of autoimmune diseases, providing new ideas for understanding the induction and development of human autoimmune diseases, as well as potential diagnosis and targeted treatment options
.
Original link: https:// Platemaker: Notice for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article, personal forwarding and sharing are welcome, and it is prohibited without permission Reprinted, the author has all legal rights, offenders must be investigated
.
Specific antibodies and cells for autoantigens, which attack the body's own cells, organs and systems and cause pathogenic damage
.
Such diseases affect nearly 10% of the world's population, seriously affecting the quality of life of patients, and severe cases can be fatal
.
Immune cells, especially B lymphocytes, play a key role in the pathogenesis of autoimmune diseases
.
However, the molecular regulation mechanism of pathogenic self-reactive B lymphocytes in the initial development stage is still poorly understood
.
Glycosylation is the main method of protein post-translational modification
.
N-type sugars and O-type sugars are the main glycosylation types of cell surface proteins, and their sugar-based components are affected by cell development stages and changes in the environment
.
Cosmc and Tsynthase are the key molecules in O-sugar synthesis pathway, knocking out either of them can completely block the synthesis and extension of O-sugar
.
In the context of autoimmune diseases, it can be expected that changes in B cell surface glycosylation will affect the induction and development of autoimmune diseases, but there has been no relevant research before
.
The Richard Cummings laboratory of the Harvard Medical School Beth Israel Deaconess Medical Center (BIDMC) published a research article titled Cosmc deficiency causes spontaneous autoimmunity by breaking B cell tolerance in Science Advances on October 6, 2021.
This study clarified B for the first time.
O-type glycation on the surface of lymphocytes is the regulation mechanism of autoimmune diseases.
Its absence breaks the immune tolerance of B lymphocytes and triggers the spontaneous development of autoimmune diseases
.
Previously, the Cummings research group had used the Cre-LoxP system to establish BC-CsomcKO mice, in which Cosmc was only deleted in B cells
.
The author found that Cosmc controls the development and homing of B cells (Zeng et al, Nat Commun.
2020)
.
In the current study, the authors further found that in BC-CosmcKO mice, a variety of lesions similar to the symptoms of human autoimmune diseases can be observed, including body weight loss, swelling and inflammation of the spleen and multiple lymph nodes, and multiple organs, including eyes.
Damage and necrosis of the body, liver and skin
.
Interestingly, this kind of disease mostly occurs in female BC-CosmcKO mice, and the sex-differentiated characteristics of this kind of disease are similar to many human autoimmune diseases
.
These lesions eventually led to the death of approximately 10% of female BC-CosmcKO mice
.
The author further used a variety of methods to prove that there are a variety of high-level expression of anti-autoantigen antibodies in BC-CosmcKO mice, and the downstream immune effectors and effector mechanisms have signs of activation, which shows that the absence of Cosmc breaks the B cell immune tolerance
.
The destruction of B cell tolerance is usually accompanied by a series of B cell development and dysfunction
.
The author further found that Cosmc-deficient B lymphocytes overreacted to a variety of antigens and combinations of antigens
.
Related to the excessive activation of Cosmc-deficient B lymphocytes is the presence of a high proportion of spontaneous germinal center B cells in a variety of lymphoid tissues in BC-CosmcKO mice, which is five to ten times higher than that of normal wild type.
In some lymphoid tissues, more than half of the B cells are germinal center B cells
.
Finally, the author analyzes the impact of the absence of Cosmc in B cells on the signal transduction of B cell receptors at the molecular level
.
It was found that the loss of Cosmc leads to an increase in the retention time of the B cell receptor (IgM) on the cell surface, which enhances a variety of downstream transduction signals
.
This indicates that the O-sugar on the cell surface controlled by Cosmc maintains its downstream signal homeostasis by regulating the endocytosis of B cell receptors under physiological conditions
.
The lack of O-type sugars, as demonstrated by the B cells of BC-CosmcKO mice, leads to the loss of B cell signal transduction and eventually various pathologies
.
Since O-sugar is easily affected by the environment, it is worth exploring whether there is a similar phenomenon in patients with autoimmune diseases
.
Richard Cummings is the titled professor of S.
Daniel Abraham of BIDMC at Harvard Medical School.
His team cloned and analyzed the Tsynthase and Cosmc genes many years ago
.
Dr.
Junwei Zeng, lecturer in the Department of Surgery, is the first author and corresponding author of the article
.
The author found for the first time that the deletion of a single gene (Cosmc) in B lymphocytes can lead to the spontaneous development of autoimmune diseases, providing new ideas for understanding the induction and development of human autoimmune diseases, as well as potential diagnosis and targeted treatment options
.
Original link: https:// Platemaker: Notice for reprinting on the 11th [Non-original article] The copyright of this article belongs to the author of the article, personal forwarding and sharing are welcome, and it is prohibited without permission Reprinted, the author has all legal rights, offenders must be investigated
.
